It is known that (2R)—N-({5-[3-(2,5-difluorophenyl)-2-(1,3-dihydro-2H-benzimidazole-2-ylidene)-3-oxopropanoyl]-2-fluorophenyl}sulfonyl)-2-hydroxypropane imide amide (hereinafter sometimes referred to as compound A) of the formula:
and its optical isomer, (2S)—N-({5-[3-(2,5-difluorophenyl)-2-(1,3-dihydro-2H-benzimidazole-2-ylidene)-3-oxopropanoyl]-2-fluorophenyl}sulfonyl)-2-hydroxypropane imide amide (hereinafter sometimes referred to as compound B), have an antagonistic activity against a gonadotropin releasing hormone (GnRH) receptor, and are useful as active ingredients of a therapeutic agent for sex hormone-dependent diseases, such as prostate cancer, benign prostatic hyperplasia, breast cancer, endometriosis, and/or uterine fibroid (Patent Literature 1). Further, compound A and a method of manufacturing the same are known (Patent Literatures 2 and 3).
With respect to the compound, in order to effectively express the pharmacological effects of the active ingredient and remit or cure indications of interest, it is necessary to select an appropriate dosage form and formulation depending on, needless to say, the pharmacological properties of the active ingredient, as well as its physicochemical properties, the type and disease state of indications of interest, and the like.
However, although a compound selected on the basis of excellent pharmacological effects is expected to exhibit fast-acting properties against its indications, it is often found to be poorly soluble. Since a poorly soluble drug also exhibits low solubility in the digestive tract, the problem is not only that the absorbability from the mucous membrane of the digestive tract is low, but also that the fast-acting properties are not expected.
Therefore, even in the current situation, formulation design to improve the solubility and the oral absorbability of a poorly soluble drug is an important technical problem for the efficacy expression of the poorly soluble drug.
Conventionally, as methods of improving the solubility and oral absorbability of a poorly soluble drug, a method in which a drug is refined, a method in which a solid dispersion is formed, or the like, are known. Among these methods, it is considered that the method in which a solid dispersion is formed is a practically versatile method to improve the solubility and oral absorbability of poorly soluble drugs (Patent Literatures 4 and 5).
Further, as a technique for improving the solubility of a poorly soluble drug, an invention in which a polymer is added to a poorly soluble drug, which can be present in either a crystalline form or an amorphous form, so that the maximum concentration of the drug becomes at least 1.25 times, is known (Patent Literature 6).
However, as compound A or a pharmaceutically acceptable salt thereof, in which the dose is 100 mg or more depending on indications, since it is necessary, when it is formulated, to take into consideration not only the improvement of solubility and oral absorbability, but also downsizing (compactification), there is room for further improvement with respect to the solubilization technique of poorly soluble drugs.